Table 1:

Anticancer drugs and adjunctive therapies commonly associated with hypertension. Listed are example drugs, hypothesized mechanisms of drug-induced hypertension, and suggested first-line treatment of hypertension.

Anticancer drug class	Example drugs	Putative mechanisms	Suggested first-line treatmenta	Ref
VEGF signalling pathway inhibitors	Bevacizumab, sorafenib, sunitinib, lenvatinib, axitinib, pazopanib, regorafinib	↑ Vasoconstriction (ET-1), ↓ vasodilation (NO), endothelial dysfunction, capillary rarefaction, ↓ lymphangiogenesis, renal injury and TMA	ACE-I/ARB, dihydropyridine CCB	[3, 9, 12, 85–89]
Proteosome inhibitors	Bortezomib, carfilzomib, ixazomib	Cellular toxicity, endothelial dysfunction, ↓ NO bioavailability, TMA	ACE-I/ARB	[18, 90, 91]
Alkylating agents	Cyclophosphamide, ifosfamide, Busulfan	Oxidative stress, endothelial dysfunction, abnormal vascular remodelling, renal injury	ACE-I/ARB, dihydropyridine CCB	[92, 93]
Platinum-based compounds	Cisplatin, carboplatin	↓ NO bioavailability, endothelial dysfunction, renal injury	ACE-I/ARB, dihydropyridine CCB	[82, 94, 95]
Nucleoside analogues	Gemcitabine	Endothelial cell damage, TMA	ACE-I/ARB	[1, 30, 96]
BTK inhibitors	Ibrutinib, acalabrutinib	↓ hsp 70, ↓ NO bioavailability, endothelial dysfunction	ACE-I/ARB, BB (nebivolol or carvedilol)	[19, 97]
BRAF/MEK inhibitors	Vemurafenib, dabrafenib, encorafenib	CD47 upregulation, ↓ cGMP, ↓ NO bioavailability	ACE-I/ARB, dihydropyridine CCB	[20, 98, 99]
Androgen synthesis inhibitors	Abiraterone, leuprolide	CYP17A inhibition with diversion of steroid precursors to mineralocorticoid production → increased fluid retention	MRA (eplerenone), diuretics	[79, 100]
Androgen receptor blockers	Enzalutamide	Endothelial dysfunction, ↓ testosterone-induced vasodilation mediated by L-type calcium channels	Dihydropyridine CCB, ACE-I/ARB, MRA	[59, 101, 102]
mTOR inhibitors	Everolimus, sirolimus	↓ VEGF bioavailability	ACE-I/ARB, dihydropyridine CCB	[103, 104]
PI3K inhibitorsb	Copanlisib	↓ NO production by inhibition of PI3K/AKT/eNOS pathway	ACE-I/ARB, dihydropyridine CCB	[26, 104]
RET kinase inhibitors	Selpercatinib, pralsetinib	Inhibition of BRAF/MEK/ERK → CD47 upregulation, ↓ cGMP, ↓ NO bioavailability	ACE-I/ARB, dihydropyridine CCB	[105–107]
PARP inhibitorsc	Niraparib	↓ Dopamine, norepinephrine and serotonin reuptake, inhibition of DYRK1A	BB (nebivolol or carvedilol), ACE-I/ARB	[108–110]
Calcineurin inhibitors	Cyclosporine, tacrolimus	↑ Proximal tubule Na reabsorption, renal dysfunction, ↓ NO bioavailability, ↑ ET-1 and ROS, ↑ RAAS	Dihydropyridine CCB, thiazide diuretics	[41, 111–113]
Glucocorticoids	Prednisone, dexamethasone	↑ Na and water retention, ↑ vasoconstriction, ↑ sensitivity to endogenous vasopressors	MRA, diuretics, ACE-I/ARB, steroid dose reduction or discontinuation	[114]
Erythropoiesis-stimulating agents	Erythropoietin, darbopoietin	↑ Blood viscosity, ↑ vasoconstriction, ↑ sensitivity to endogenous vasopressors	Dihydropyridine CCB, EPO discontinuation	[38]

^aIn the absence of contraindication.

^bIdelalisib does not typically cause hypertension.

^cOlaparib may have antihypertensive and cardioprotective effects.

ET-1, endothelin 1; hsp, heat shock protein; CD47, cluster of differentiation; cGMP, cyclic guanosine monophosphate; CYP17A, cytochrome 17A; DYRK1A, dual-specificity tyrosine phosphorylated and regulated kinase 1A; Na, sodium; EPO, erythropoietin.